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Abstract Background Nationwide restrictions and recommendations from the Association of American Medical Colleges mandated program directors to conduct all graduate medical education interviews virtually in the Spring of 2020 in response to the COVID-19 pandemic. This study was conducted to assess the impact of virtual interviews on a candidates’ ability to effectively create a rank list. Objective The primary objective of this study was to evaluate Obstetrics and Gynecology (ObGyn) subspecialty fellowship applicants’ perspectives regarding the effectiveness of virtual interviews for creating a rank list. Secondary outcomes included perceived advantages and disadvantages of the process and costs of the process. Methods This was a cross-sectional IRB-exempt study, using an electronic survey administered to a convenience sample of applicants to ObGyn subspecialty fellowship programs. The survey was administered via RedCap between the rank list submission deadline and the Match. Descriptive statistics were used. Results Response rate was 158/330 (48%). Overall, 129/158 (82%) percent of respondents felt confident in making their rank list based on the virtual interviews, and 146/158 (92%) were “very satisfied” or “somewhat satisfied” with the process. Of those who expressed an interview style preference, 65/149(44%) of respondents preferred virtual interviews; 49/149(33%) had no preference or were not sure. Nearly all 146/148(99%) applicants cited cost-savings as a distinct advantage of virtual interviews. Conclusion Applicants to ObGyn subspecialty fellowships felt comfortable to create a rank list based on the virtual interview. This study indicates that the virtual format is effective, less stressful and less costly for ObGyn subspecialty interviews and should be considered beyond the pandemic to remove barriers and burdens for applicants.

Objective To explore core elements from Teachers’ Relational Competence in general practice literature regarding building relationships in consultations, specifying actions doctors take to create and maintain relationship quality with patients. This systematic literature review aims to map and propose a similar framework for the doctor-patient relationship.Background The doctor-patient relationship, a well-researched yet complex field, often lacks clear descriptions. In recent definitions of patient-centred medicine, the responsibility of this relationship falls on the doctor, though how both relationship and responsibility is enacted needs clarification. Pedagogical literature on the student-teacher relationship provides a framework for relational competence, incorporating the needs and interactions between teacher and student and their alignment with institutional goals.Methods A systematic review of two databases yielded 1256 hits. After screening, 15 studies were included and assessed. A qualitative synthesis was conducted through iterative and thematic deductive analysis.Results Four relationally competent attitudes identified were: Attention to emotion, Devotion, Mentalization, and Time-oriented presence. Four relationally competent actions identitfied were: Being open, Attunement, Offering Support, and Using humor. Additionally, Trust and Continued connectedness were found as components of both attitudes and actions.Conclusion An explanatory framework for professional relational competence for GPs includes concrete actions and specific attitudes before and during consultations. These consist of four key attitudes and four categories of actions with several subgroups of actions. Two additional components to the framework was found.

Objective To explore possible challenges to General Practitioners’ (GPs’) interpersonal contact with patients in video consultations (VCs), and learn how they change their communication strategies to carry out medical work in a setting with altered sensory conditions.Design, setting, subjects The study included 6 GPs from the Copenhagen area, with different levels of experience of VC. The data consist of 6 interviews with GPs, held in 2021-2022. The semi-structured interviews included playback of a recorded VC between each GP and a patient, inspired by the Video-Stimulated Interview technique. Interviews were transcribed and analyzed using Interpretative Phenomenological Analysis (IPA).Results GPs experienced alterations in the sensation of their patients in VCs, and worried about missing something important, including assessing the patient. Generally, GPs felt that interpersonal contact was good enough for the purpose. GPs compensated for altered sensory conditions on video by asking more questions, repeating their advice, and meta-communicating. They used their senses of sight and hearing relatively more in VCs. Compensation also took the form of triage, so that consultations on sensitive topics or with new patients were not selected to take place on video.Conclusion and implications By compensating for altered sensory conditions in VCs, GPs can carry out their medical work sufficiently well and sustain the best possible interpersonal contact. Our findings are useful for establishing ways to maintain good interpersonal contact between GPs and patients in VCs.

Background Experience-based knowing in general practice includes advanced interpretation of subjective, complex and particular phenomena in a social context. Enabling different metapositions for reflexivity may provide the accountability needed for such knowing to be recognized as evidence-based practice.Objective To demonstrate and discuss the potential of substantive theories to enhance interpretation of complex challenges in clinical knowing in general practice.Methods We present a fictional case to demonstrate how interdisciplinary substantive theories, with a relevant and specific match to concrete questions, can situate the clinical interaction at an accountable platform. A female patient with Parkinson’s disease consults her GP complaining that the disease is restraining her life and threatening her future. The GP has some new ideas from Bandura’s theory of self-efficacy and introduces the patient to strategies for further action.Findings The case presents an example of how a relevant substantive theory may offer the GP: 1) a sharper focus for achievement: recognising the issues of fear and identity in chronic, progressive illness, 2) a subsequent position for individualized understanding of adequate strategies: encouraging physical and social activity in a well-known context, and 3) an invitation to consider further possibilities: finding ways to alleviate the burden of fear and progressive decline; engaging in joyful living.Implications General practice knowledge embraces a diversity of sources with different evidence power. The transparency mediated to clinical practice when supported by relevant substantive theories may contribute to recognition of experience-based knowing as evidence-based practice.

Abstract Background Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight

AbstractObjective To analyse the mechanisms at play in the adjudications made by professionals and socially vulnerable patients with type 2 diabetes about their eligibility for care.Design, setting and subjects The study included 14 patients and 10 health professionals in seven general practice surgeries in deprived areas in Greater Copenhagen. The study data consist of 17 semi-structured interviews with patients and 22 with health professionals immediately after observation of 23 consultations. Our analytical approach was inspired by Systematic Text Condensation and the concept of ‘candidacy’ for access to health care.Results Adjudications of patients not being candidates for services were common, but we also found that both patients and health professionals worked to align the services to the needs of the patients. This could include using services differently than was intended by the providers or by changing routines to make it easier for patients to use the services. We discuss these processes as ‘tinkering’. This usually implies that the best individual solution for the patient is aimed for, and in this study, the best solution sometimes meant not focusing on diabetes.Conclusion The study adds to existing knowledge about access to services for socially vulnerable patients by demonstrating that both patients and professionals in general practice engage in tinkering processes to make services work.

AbstractThis study investigates the influence of lecturer non-verbal cues on student perceptions of teaching quality, considering the moderating effects of gender and age. Non-verbal communication is crucial in instructional settings, impacting students’ engagement, learning experiences, and overall perceptions of teaching effectiveness. Drawing on the social identity theory, the study explores the relationships between specific non-verbal cues displayed by lecturers and students’ perceptions of teaching quality. A quantitative research design is employed, comprising questionnaires. The participants include 614 students from various Technical University education programs, selected using the Google Form. The questionnaires assess students’ perceptions of lecturer non-verbal cues and teaching quality, with Likert scale items (i.e. 1. Strongly disagree to 5. Strongly agree) providing quantitative data. Quantitative analysis reveals significant associations between non-verbal cues such as facial expressions and gestures, and positive teaching quality perceptions. Moreover, gender and age are identified as moderators, affecting students’ interpretations of non-verbal cues and subsequent evaluations of teaching quality; however, students do not place much emphasis on these two variables. The findings contribute to instructional communication theory, advancing the understanding of how non-verbal communication influences teaching effectiveness.

Abstract Objective Few patients achieve full control of their coronary artery disease (CAD) risk factors. Follow-up, such as cardiac rehabilitation, is important to increase adherence to lifestyle changes and treatment, to improve the patient’s risk profile, and to treat established complications of CAD clinical events. However, the type of follow-up patients receive varies. Therefore, the aim of this research note was to describe and compare patients’ self-reported use of health services, the type of follow-up patients reported to prefer, and the type of information patients reported to be important, in two countries with different follow-up practices after PCI. Results We included 3417 patients in Norway and Denmark, countries with different follow-up strategies after PCI. The results showed large differences between the countries regarding health services used. In Denmark the most frequently used health services were consultations at outpatient clinics followed by visits to the general practitioner and visits to the fitness centre, whereas in Norway visits to the general practitioner were most common, followed by rehospitalisation and no follow-up used. However, patients found the same type of follow-up and information important in both countries. Patients’ perceived need for follow-up and information decreased over time, suggesting a need for early follow-up when the patients are motivated. Trial registration: NCT03810612 (18/01/2019).

Introduction Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.Methods and analysis In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.Ethics and dissemination The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.Trial registration number NCT05676541.

Abstract Introduction: Recruitment of participants into research studies remains a major concern for investigators. Using clinical teams to identify potentially eligible patients can present a significant barrier. To overcome this, we implemented a process for using our patient portal, called MyChart, as a new institutional recruitment option utilizing our electronic health record’s existing functionality. Methods: To streamline the institutional approval process, we established a working group comprised of representatives from human subject protection, information technology, and privacy and vetted our process with many stakeholder groups. Our specific process for study approval is described and started with a consultation with our recruitment and retention function funded through our Clinical and Translational Science Award. Results: The time from consultation to the first message(s) sent ranged from 84 to 442 days and declined slightly over time. The overall patient response rate to MyChart messages about available research studies was 23% with one third of those saying they were interested in learning more. The response rate for Black and Hispanic patients was about 50% that of White patients. Conclusions: Many different types of studies from any medical specialty successfully identified interested patients using this option. Study teams needed support in defining appropriate inclusion/exclusion criteria to identify the relevant population in the electronic health records and they needed assistance writing study descriptions in plain language. Using MyChart for recruitment addressed a critical barrier and opened up the opportunity to provide a full recruitment consultation to identify additional recruitment channels the study teams would not have considered otherwise.

Enrollment into a prospective cohort study of mother–preterm infant dyads during the COVID-19 pandemic progressed slower than anticipated. Enrollment occurred during the first week after preterm birth, while infants were still hospitalized. We hypothesized that slower enrollment was attributable to mothers testing positive for COVID-19 as hospital policies restricted them from entering the neonatal intensive care unit, thus reducing interactions with research staff. However, only 4.5% of 245 screened mothers tested COVID-19 positive. Only 24.9% of those screened, far fewer than anticipated, were eligible for enrollment. Assumptions about pandemic-related enrollment barriers were not substantiated in this pediatric cohort.

This article presents a landscape assessment of the findings from the 2021 Clinical and Translational Science Award (CTSA) Evaluators Survey. This survey was the most recent iteration of a well established, national, peer-led systematic snapshot of the CTSA evaluators, their skillsets, listed evaluation resources, preferred methods, and identified best practices. Three questions guided our study: who are the CTSA evaluators, what competencies do they share and how is their work used within hubs. We describe our survey process (logistics of development, deployment, and differences in historical context with prior instruments); and present its main findings. We provide specific recommendations for evaluation practice in two main categories (National vs Group-level) including, among others, the need for a national, strategic plan for evaluation as well as enhanced mentoring and training of the next generation of evaluators. Although based on the challenges and opportunities currently within the CTSA Consortium, takeaways from this study constitute important lessons with potential for application in other large evaluation consortia. To our knowledge, this is the first time 2021 survey findings are disseminated widely, to increase transparency of the CTSA evaluators' work and to motivate conversations within hub and beyond, as to how best to leverage existent evaluative capacity.

BackgroundThis study examined the correlation of classroom ventilation (air exchanges per hour (ACH)) and exposure to CO2 ≥1,000 ppm with the incidence of SARS-CoV-2 over a 20-month period in a specialized school for students with intellectual and developmental disabilities (IDD). These students were at a higher risk of respiratory infection from SARS-CoV-2 due to challenges in tolerating mitigation measures (e.g. masking). One in-school measure proposed to help mitigate the risk of SARS-CoV-2 infection in schools is increased ventilation.MethodsWe established a community-engaged research partnership between the University of Rochester and the Mary Cariola Center school for students with IDD. Ambient CO2 levels were measured in 100 school rooms, and air changes per hour (ACH) were calculated. The number of SARS-CoV-2 cases for each room was collected over 20 months.Results97% of rooms had an estimated ACH ≤4.0, with 7% having CO2 levels ≥2,000 ppm for up to 3 hours per school day. A statistically significant correlation was found between the time that a room had CO2 levels ≥1,000 ppm and SARS-CoV-2 PCR tests normalized to room occupancy, accounting for 43% of the variance. No statistically significant correlation was found for room ACH and per-room SARS-CoV-2 cases. Rooms with ventilation systems using MERV-13 filters had lower SARS-CoV-2-positive PCR counts. These findings led to ongoing efforts to upgrade the ventilation systems in this community-engaged research project.ConclusionsThere was a statistically significant correlation between the total time of room CO2 concentrations ≥1,000 and SARS-CoV-2 cases in an IDD school. Merv-13 filters appear to decrease the incidence of SARS-CoV-2 infection. This research partnership identified areas for improving in-school ventilation.

Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

There is still much debate about the exact nature and frequency of developmental dyscalculia, and about how it should be defined. This article examines several key questions in turn: Is developmental dyscalculia a distinct disorder, or should it be seen as the lower end of a continuum—or possibly more than one continuum—of numerical ability? Do individuals with developmental dyscalculia show atypical brain structure or function? Does the study of acquired dyscalculia have anything to teach us about developmental dyscalculia? In studying dyscalculia, should we look less at arithmetical ability as a single entity, and more at separable components of arithmetical ability? How heterogeneous is developmental dyscalculia, and how important is it to study individual profiles? To what extent is developmental dyscalculia influenced by domain-specific versus domain-general abilities? The conclusion is that, though a significant amount has been discovered through existing research, and though this has some important implications for screening and diagnosis of dyscalculia, there is much more research that still needs to be conducted if we are to answer all of these questions fully. In particular, the study of developmental dyscalculia must be more integrated with the study of individual differences in mathematics in the population as a whole.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a 6-CTSA Rockefeller-led collaboration to developcustom REDCap infrastructure to collect participant feedback using the validated Research Participant Perception Survey (RPPS), demonstrate its value in use cases, and disseminate it for broad adoption. METHODS/STUDY POPULATION: The EPV team developed data and survey implementation standards, and specifications for the dashboard and multi-lingual RPPS/REDCap project XML file. The VUMC built a custom At-a-Glance Dashboard external module that displays Top Box scores (percent best answer), with conditional formatting to aid analysis, and response/completion rates. Results populate site dashboards, and aggregate to a multi-site dashboard for benchmarking. Results can be filtered by participant/study characteristics. Sites developed individual use cases, leveraging local infrastructure, initiatives and stakeholder input. Infrastructure and guides were designed for dissemination through public websites. RESULTS/ANTICIPATED RESULTS: Five sites sent 23,797surveys via email, patient portal or SMS. 4,133 (19%) participants diverse in age, race, and ethnicity, returned responses. Sites analyzed their data and acted on selected findings, improving recruitment, communication and feeling valued. Aggregate scores for feeling listened to and respected were hight (>90%%); scores for feeling prepared by the consent process were lower (57-77%) and require action. Some groups experiences were better than others. Sites differed significantly in some scores. Dissemination of EPV is underway. Infrastructure and guides are downloadable free of charge, with advice from the EPV team. In 2023, a sixth site began piloting a lower literacy survey version and syncing data to the consortium dashboard. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to collect participant feedback, identify actionable findings and benchmark with peers. Stakeholders and collaborators designed and tested local initiatives to increase responses and diversity, address disparities, and discover better practices.

Background Out-of-hospital cardiac arrest (OHCA) and life-threatening bleeding from trauma are leading causes of preventable mortality globally. Early intervention from bystanders can play a pivotal role in increasing the survival rate of victims. While great efforts for bystander training have yielded positive results in high-income countries, the same has not been replicated in low and middle-income countries (LMICs) due to resources constraints. This article describes a replicable implementation model of a nationwide program, aimed at empowering 10 million bystanders with basic knowledge and skills of hands-only cardiopulmonary resuscitation (CPR) and bleeding control in a resource-limited setting.Methods Using the EPIS (Exploration, Preparation, Implementation and Sustainment) framework, we describe the application of a national bystander training program, named ‘Pakistan Life Savers Programme (PLSP)’, in an LMIC. We discuss the opportunities and challenges faced during each phase of the program’s implementation and identify feasible and sustainable actions to make them reproducible in similar low-resource settings.Results A high mortality rate owing to OHCA and traumatic life-threatening bleeding was identified as a national issue in Pakistan. After intensive discussions during the exploration phase, PLSP was chosen as a potential solution. The preparation phase oversaw the logistical administration of the program and highlighted avenues using minimal resources to attain maximum outreach. National implementation of bystander training started as a pilot in suburban schools and expanded to other institutions, with 127 833 bystanders trained to date. Sustainability of the program was targeted through its addition in a single national curriculum taught in schools and the development of a cohesive collaborative network with entities sharing similar goals.Conclusion This article provides a methodological framework of implementing a national intervention based on bystander response. Such programs can increase bystander willingness and confidence in performing CPR and bleeding control, decreasing preventable deaths in countries having a high mortality burden.Level of evidence Level VI.

Research on typically developing children and adults and people with developmental and acquired dyscalculia converges in indicating that arithmetical ability is not unitary but is made up of many different components. Categories of components include non-symbolic quantity representation and processing; symbolic quantity representation and processing; counting procedures and principles; arithmetic operations; arithmetical knowledge and understanding; multiple forms and applications of conceptual knowledge of arithmetic; and domain-general abilities such as attention, executive functions and working memory. There is much evidence that different components can and often do show considerable functional independence, not only in developmental and acquired dyscalculia, but in typically achieving children and adults. At the same time, it is possible to find complex interactions and bidirectional relationships between the different components, including between domain-specific and apparently domain-general abilities. There is a great deal that still needs to be discovered. In particular, we need to learn more about the origins in infancy of subitizing and approximate magnitude comparison, the extent to which these interact, the extent to which they may be further divisible, and the extent and ways in which they themselves may develop with age and the extent to which they may influence later-developing components. There also needs to be a lot more research on exactly how domain-general and domain-specific abilities contribute to mathematical development, and how they interact with one another.

Endoplasmic reticulum stress activates the unfolded protein response (UPR). The authors show that glucose extends the lifespan of aged animals by activating the otherwise quiescent UPR while causing a UPR-dependent reduced longevity in young animals

Introduction:In vitro approaches are an essential tool in screening for toxicity of new chemicals, products and therapeutics. To increase the reproducibility and human relevance of these in vitro assessments, it is advocated to remove animal-derived products such as foetal bovine serum (FBS) from the cell culture system. Currently, FBS is routinely used as a supplement in cell culture medium, but batch-to-batch variability may introduce inconsistency in inter- and intra-lab assessments. Several chemically defined serum replacements (CDSR) have been developed to provide an alternative to FBS, but not every cell line adapts easily and successfully to CDSR-supplemented medium, and the long-term effect on cell characteristics remains uncertain.Aim: The aim of this study was to adapt the TK6 cell line to animal-product free CDSR-supplemented medium and evaluate the long-term effects on cell health, growth, morphology, phenotype, and function. This included a provisional assessment to determine the suitability of the transitioned cell line for standardised genotoxicity testing using the “in vitro mammalian cell micronucleus test” (OECD TG 487).Materials and methods: Gradual adaptation and direct adaptation methodologies were compared by assessing the cell proliferation, size and viability every passage until the cells were fully adapted to animal-free CDSR. The metabolic activity and membrane integrity was assessed every 4-8 passages by PrestoBlue and CytoTox-ONE™ Homogeneous Membrane Integrity Assay respectively. A detailed morphology study by high content imaging was performed and the expression of cell surface markers (CD19 and CD20) was conducted via flow cytometry to assess the potential for phenotypic drift during longer term culture of TK6 in animal-free conditions. Finally, functionality of cells in the OECD TG 487 assay was evaluated.Results: The baseline characteristics of TK6 cells cultured in FBS-supplemented medium were established and variability among passages was used to set up acceptance criteria for CDSR adapted cells. TK6 were adapted to CDSR supplemented medium either via direct or gradual transition reducing from 10% v/v FBS to 0% v/v FBS. The cell growth rate was compromised in the direct adaptation and therefore the gradual adaptation was preferred to investigate the long-term effects of animal-free CDSR on TK6 cells. The new animal cells showed comparable (p > 0.05) viability and cell size as the parent FBS-supplemented cells, with the exception of growth rate. The new animal free cells showed a lag phase double the length of the original cells. Cell morphology (cellular and nuclear area, sphericity) and phenotype (CD19 and CD20 surface markers) were in line (p > 0.05) with the original cells. The new cells cultured in CDSR-supplemented medium performed satisfactory in a pilot OECD TG 487 assay with compounds not requiring metabolic activation.Conclusion: TK6 cells were successfully transitioned to FBS- and animal product-free medium. The new cell cultures were viable and mimicked the characteristics of FBS-cultured cells. The gradual transition methodology utilised in this study can also be applied to other cell lines of interest. Maintaining cells in CDSR-supplemented medium eliminates variability from FBS, which in turn is likely to increase the reproducibility of in vitro experiments. Furthermore, removal of animal derived products from cell culture techniques is likely to increase the human relevance of in vitro methodologies.

Abstract Background Adherence and completion of programmes in educational and physical exercise sessions is essential in cardiac rehabilitation (CR) to obtain the known benefits on morbidity, mortality, risk factors, lifestyle, and quality of life. The patient education strategy “Learning and Coping” (LC) has been reported to positively impact adherence and completion in a hospital setting. It is unknown if LC has impact on adherence in primary healthcare settings, and whether LC improves self-management. The aim of this pragmatic primary healthcare-based study was to examine whether patients attending CR based on LC had a better adherence to patient education and physical exercise, higher program completion rate, and better self-management compared to patients attending CR based on a consultation program Empowerment, Motivation and Medical Adherence (EMMA). Method A pragmatic cluster-controlled trial of two types of patient education LC and EMMA including ten primary healthcare settings and 514 patients (LC, n = 266; EMMA, n = 248) diagnosed with ischaemic heart disease discharged from hospital and referred to CR between August 1, 2018 and July 31, 2019. Adherence was defined as participation in ≥ 75% of provided sessions. Completion was defined as patients attended the final interview at the end of the 12-weeks programme. Patient Activation Measure (PAM) was used to obtain information on a person's knowledge, skills and confidence for self-management. PAM questionnaire was completed at baseline and 12-weeks follow-up. Multiple and Linear regression analyses adjusted for potential confounder variables and cluster effect were performed. Result Patients who followed CR based on LC had a higher adherence rate to educational and physical exercise sessions compared to patients who followed CR based on EMMA (p 0.05). At 12-weeks, there was no statistical differences in PAM-score between clusters (p > 0.05). Conclusion This study indicates that the LC positively impacts adherence in CR compared to EMMA. We found non-significant difference in completing CR and in patient self-management between the two types of patient education. Future studies are needed to investigate if the higher adherence rate achieved by LC in primary healthcare settings translates into better health outcomes.

Abstract Pulmonary hypertension associated with bronchopulmonary dysplasia is a severe complication of preterm birth resulting in high mortality of up to 50% within the first 2 years of life. There is a direct relationship between bronchopulmonary dysplasia severity and incidence of associated pulmonary hypertension. However, it is challenging to clinically characterize severe bronchopulmonary dysplasia with and without pulmonary hypertension and there is need for better understanding of the two entities. Our main objective is to identify markers to help understand biological processes and characterize infants with pulmonary hypertension associated with bronchopulmonary dysplasia using tracheal aspirates. We conducted an unbiased multiomic analysis of tracheal aspirates via microRNA (miRNA) polymerase chain reaction arrays, RNA sequencing, and mass spectrometry proteomics in preterm infants with severe bronchopulmonary dysplasia with and without pulmonary hypertension (n = 46). Our pilot study analysis revealed 12 miRNAs (hsa‐miR‐29a, has‐miR‐542‐3p, has‐miR‐624, has‐miR‐183, hsa‐miR‐501‐3p, hsa‐miR‐101, hsa‐miR‐3131, hsa‐miR‐3683, hsa‐miR‐3193, hsa‐miR‐3672, hsa‐miR‐3128, and hsa‐miR‐1287), 6 transcripts (IL6, RPL35P5, HSD3B7, RNA5SP215, OR2A1‐AS1, and RNVU1‐19), and 5 proteins (CAPS, AAT, KRT5, SFTPB, and LGALS3BP) with significant differential expression in preterm infants with severe lung disease with pulmonary hypertension when compared with infants with severe lung disease but no pulmonary hypertension. Pathway analysis of the integrated multiomic expression signatures revealed NFkB, VEGF, SERPINA1, IL6, and ERK1/2 as target molecules and cellular development, cellular growth and proliferation, and cellular movement as key affected molecular functions. Our multiomic analysis of tracheal aspirates revealed a comprehensive thumbprint of miRNAs, mRNAs, and proteins that could help endotype infants with severe lung disease and pulmonary hypertension.

The suspension of face-to-face teaching, due to the COVID-19 social distancing regulations, raised serious concerns about the impacts on children’s academic learning. Because the implementation of distance education in Germany was entirely the responsibility of individual schools, and because the home learning environments varied across households, school children had very different learning conditions during the pandemic. This fact raises questions whether the conditions of distance learning has impacted children’s development of basic number skills. In this paper, descriptive information on children’s home learning conditions and teachers’ distance teaching approaches during the pandemic, socio-cultural capital, and basic number skills of 484 third and fourth grade students (51.2% girls) in the state of North Rhine-Westphalia (Germany) are assessed. The data revealed risk factors such as not having a tablet/laptop, lack of access to the internet, or a learning environment with siblings without an adult family member present. A negative association was found between multiple risk factors (at-risk levels) in home learning and basic number skills. This link was partially mediated by socio-cultural capital and moderated by teachers’ distance teaching approach. Children whose teachers applied a more personalized teaching approach showed fewer negative relations between at-risk levels and basic number skills. While no evidence was observed for positive effects of videoconferencing, school-based emergency classes, or private tutoring on basic number skills, children whose learning was supported by learning management systems showed better skills than their peers. The findings highlight the differential impact of home-based learning conditions during the pandemic and provide practical implications for realization of distance teaching.

The aim of this study was to identify the types of reflective writing produced by a cohort of medical students undertaking a clinical psychiatry module as part of their undergraduate medical programme at a University in the Republic of Ireland. A random sample of 80 reflective essays were selected for review. These assignments were evaluated using a comprehensive content analysis process with a pre-determined reflective writing coding instrument and coding protocol. Dialogic reflection was the most common type of reflective writing identified, with 56.3% (n = 45) of the summative assignments categorised as such. Twenty five percent (n = 20) of the assignments were classified as descriptive reflection, while 18.8% (n = 15) of the assignments demonstrated critical reflection. Overall, the findings of the study indicate that this innovative programme was successful in fostering and developing reflective writing in medical students to quite an advanced level. The paper concludes with specific recommendations for facilitating reflective writing in professional and higher education.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a Rockefeller-led 6-CTSA consortium that aims to collect research participant feedback through new Research Participant Perception Survey (RPPS)/REDCap infrastructure and data aggregation to a national database. Here we describe diverse Use Cases and launch dissemination to other hubs. METHODS/STUDY POPULATION: The EPV team refined the RPPS-S and developed fielding and data standards, a multi-lingual RPPS/REDCap project XML, At-a-Glance Dashboard, EPV Consortium Database, and Use Cases to align with local initiatives and stakeholder input. Sites ran full thread tests of the infrastructure before launch. To demonstrate RPPS/REDCap, 5 sites implemented Use Cases, surveyed diverse populations via email, patient portal or SMS, and analyzed results using the At-a-Glance Dashboard External module (which provides visual analytics and enables filtering by participant/study characteristics). Sites continue to collect, synthesize and respond to actionable data. To disseminate infrastructure, we will invite early adopters to implement the RPPS/REDCap infrastructure locally, joining the EPV learning collective. RESULTS/ANTICIPATED RESULTS: To date, 5 sites surveyed 10,199 research participants, at post-consent or end of study. 2833 (26%) research participants responded, from diverse demographic groups. More than 90% gave the Top Box score response regarding courtesy, respect for cultural background, privacy, and lack of pressure to join a study. Disparities were apparent in the informed consent experience, with a Top Box score range of 38-78% in different demographics. Dissatisfaction with out-of-pocket research costs was a recurring theme. Top Box scores varied for feeling like a valued partner in research (69-93%), would recommend research participation to friends or family (56%-81%), and Overall Experience (64%-90%) questions. Sites identified actionable findings in areas of consent, communication, partnership, and study conduct. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to broadly collect participant feedback, identify actionable findings and make inter-institutional comparisons. Collaborators are designing local initiatives to increase response rate and diversity, address disparities in research participation experiences, and discover better practices.

Abstract Micronucleus (MN) assessment is a valuable tool in safety assessment. However, several compounds are positive in the in vivo bone marrow (BM) MN assay but negative in vitro, reflecting that BM complexity is not recapitulated in vitro. Importantly, these compounds are not genotoxic; rather, drug-driven pharmacological-effects on the BM increase MN, however, without mechanistic understanding, in vivo positives stop drug-progression. Thus, physiologically-relevant BM models are required to bridge the gap between in vitro and in vivo. The current study aimed to investigate the utility of two human 3D BM models (fluidic and static) for MN assessment. MN induction following treatment with etoposide and Poly-ADP Ribose Polymerase inhibitor (PARPi) and prednisolone (negative in vitro, positive in vivo) was determined in 2D L5178Y and human BM cells, and the 3D BM models. Etoposide (0–0.070 µM) and PARPi (0–150 µM) induced MN in both 3D BM models indicating their utility for genotoxicity testing. Interestingly, PARPi treatment induced a MN trend in 3D more comparable to in vivo. Importantly, prednisolone (0–1.7 mM) induced MN in both 3D BM models, suggesting recapitulation of the in vivo microenvironment. These models could provide a valuable tool to follow up, and eventually predict, suspected pharmacological mechanisms, thereby reducing animal studies.

Abstract Background Type 2 diabetes cluster in lower social groups and people with type 2 diabetes from lower social groups experience more complications, benefit less from health services and live shorter lives than people with type 2 diabetes from higher social groups. Different logics govern diabetes care and potentially influence the possibility of socially vulnerable type 2 diabetes patients to access and benefit from health services. In order to understand which practice and underlying logic enable socially vulnerable type 2 diabetes patients to access and benefit from diabetes care we aim to describe what professionals at a specialized diabetes clinic do to adjust services to patient’s needs and make the tasks involved in diabetes care doable for socially vulnerable patients and how this work is embedded in an organizational and moral context. Methods Ethnographic fieldwork combining participant observation and interviews was carried out between February 2017 and March 2018 in a specialized diabetes clinic located in a socially deprived area in the capital region of Denmark. Sixteen patients (9 male, 7 female, aged 35-73 years) and 12 professionals (7 doctors, 4 nurses, 1 secretary) participated in the study. We used Annemarie Mol’s concept of “the logic of care” to guide our analysis. Results Our analysis shows that the logic of care and the care practices in this clinic are characterized by a needs-based approach to treatment involving adjustment of services (permeability, timing, and content) and seeing the patient as a person with many needs. Throughout our description of selected care practices, we both characterize how health professionals practice this particular logic of care and the organizational and normative conditions that this logic is entangled with. Conclusions Practicing diabetes care based on patients’ needs involves individualization, something often described as an element of patient centred care. Our study shows that this ideal of individualization and adjustment of treatment is possible in practice. Organizational flexibility and an organizational culture that values patient needs enable needs-based care. In order for socially vulnerable type 2 diabetes patients to benefit from health services it is necessary to create conditions under which professionals can attend to these patients’ multiple and complex needs. Adjusting care to these needs demand a variety of professional efforts some of which are hardly predictable or standardisable.

Breast ultrasound provides a first-line evaluation for breast masses, but the majority of the world lacks access to any form of diagnostic imaging. In this pilot study, we assessed the combination of artificial intelligence (Samsung S-Detect for Breast) with volume sweep imaging (VSI) ultrasound scans to evaluate the possibility of inexpensive, fully automated breast ultrasound acquisition and preliminary interpretation without an experienced sonographer or radiologist. This study was conducted using examinations from a curated data set from a previously published clinical study of breast VSI. Examinations in this data set were obtained by medical students without prior ultrasound experience who performed VSI using a portable Butterfly iQ ultrasound probe. Standard of care ultrasound exams were performed concurrently by an experienced sonographer using a high-end ultrasound machine. Expert-selected VSI images and standard of care images were input into S-Detect which output mass features and classification as "possibly benign" and "possibly malignant." Subsequent comparison of the S-Detect VSI report was made between 1) the standard of care ultrasound report by an expert radiologist, 2) the standard of care ultrasound S-Detect report, 3) the VSI report by an expert radiologist, and 4) the pathological diagnosis. There were 115 masses analyzed by S-Detect from the curated data set. There was substantial agreement of the S-Detect interpretation of VSI among cancers, cysts, fibroadenomas, and lipomas to the expert standard of care ultrasound report (Cohen's κ = 0.73 (0.57-0.9 95% CI), p

Objective To explore how agenda navigation may be accomplished underway in consultations covering multiple topics, we identified and analyzed one GP’s communicative strategies. Design, setting, and subjects A qualitative observational case study with linguistic microanalysis of an exemplary consultation between a female patient with diabetes and her male GP. We used speech act theory to identify communicative actions that indicated agenda navigation by the GP in transitions between episodes concerning ten topics. Results Microanalysis revealed different aspects of agenda navigation by the GP using speech acts, especially ways of opening or closing an episode. The opening of episodes was characterized by speech acts accepting the patient’s request to discuss a topic, mostly at the beginning of the consultation. Speech acts to inform or to request information from the patient dominated later in the consultation. The GP closed all episodes using speech acts to instruct or appraise the patient, or to make agreements and plans. Conclusion and practice implications Skilful agenda navigation is an important tool for consultations covering multiple issues and could be further developed for medical education. The opening and closing of episodes were vital communicative strategies supporting patient-centered communication in a complex consultation while maintaining the focus of the consultation agenda.KEY POINTS While traditional consultation models cover one health problem, GP consultations often include many patient issues in each session. Linguistic microanalysis of speech acts helped to identify communication strategies in a GP consultation with multiple topics. The GP conducted agenda navigation by distinctly opening and closing episodes concerning specific topics. Episodes were opened by accepting, informing, and requesting and closed by instruction, appraisal, making agreements, or plans.

Background: Social determinants of health directly affect cancer survival. Driven by advances in technology and recent demands due to COVID-19, telemedicine has the ability to improve patient access to care, lower health care costs, and increase workflow efficiency. The role of telemedicine in radiation oncology is not established. Materials and Methods: We conducted an IRB-approved pilot trial using a telehealth platform for the first post-radiation visit in patients with any cancer diagnosis. The primary endpoint was feasibility of using telehealth defined by completion of five telehealth visits per month in a single department. Secondary endpoints included the ability to assess patients appropriately, patient and physician satisfaction. Physicians were surveyed again during the pandemic to determine whether viewpoints changed. Results: Between May 27, 2016 and August 1, 2018, 37 patients were enrolled in the Telehealth in Post-operative Radiation Therapy (TelePORT) trial, with 24 evaluable patients who completed their scheduled telehealth visit. On average, 1.4 patients were accrued per month. All patients were satisfied with their care, had enough time with their physician and 85.7% believed the telehealth communication was excellent. All physicians were able to accurately assess the patient's symptoms via telehealth, whereas 82.3% felt they could accurately assess treatment-related toxicity. Physicians assessing skin toxicity from breast radiation were those who did not feel they were able to assess toxicity. Discussion and Conclusions: Both health care providers and patients have identified telemedicine as a suitable platform for radiation oncology visits. Although there are limitations, telemedicine has significant potential for increasing access of cancer care delivery in radiation oncology.

Abstract Background Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. Three subtypes of endometriosis exist, with ~ 80% of women having superficial peritoneal endometriosis (SPE). Endometriosis is diagnosed by laparoscopy and, if SPE is found, gynaecologists usually remove it surgically. However, many women get limited pain relief from surgical removal of SPE. We plan to undertake a future large trial where women who have only SPE found at initial laparoscopy are randomly allocated to have surgical removal (excision or ablation) of SPE, or not. Ultimately, we want to determine whether surgical removal improves overall symptoms and quality of life, or whether surgery is of no benefit, exacerbates symptoms, or even causes harm. The primary objective of this feasibility study is to determine what proportion of women with suspected SPE undergoing diagnostic laparoscopy will agree to randomisation. The secondary objectives are to determine if there are differences in key prognostic parameters between eligible women that agree to be randomised and those that decline; how many women having laparoscopy for investigation of chronic pelvic pain are eligible for the trial; the range of treatment effects and variability in outcomes and the most acceptable methods of recruitment, randomisation and assessment tools. Methods We will recruit up to 90 women with suspected SPE undergoing diagnostic laparoscopy over a 9-month recruitment period in four Scottish hospitals and randomise them 1:1 to either diagnostic laparoscopy alone (with a sham port to achieve blinding of the allocation) or surgical removal of endometriosis. Baseline characteristics, e.g. age, index of social deprivation, ethnicity, and intensity/duration of pain will be collected. Participants will be followed up by online questionnaires assessing pain, physical and emotional function at baseline, 3 months, 6 months and 12 months. Discussion Recruitment to a randomised controlled trial to assess the effectiveness of surgery for endometriosis may be challenging because of preconceived ideas about treatment success amongst patients and clinicians. We have designed this study to assess feasibility of recruitment and to inform the design of our future definitive trial. Trial registration ClincicalTrials.gov, NCT04081532 Status Recruiting

Abstract To provide a comprehensive analysis of small molecule genotoxic potential we have developed and validated an automated, high-content, high throughput, image-based in vitro Micronucleus (IVM) assay. This assay simultaneously assesses micronuclei and multiple additional cellular markers associated with genotoxicity. Acoustic dosing (≤ 2 mg) of compound is followed by a 24-h treatment and a 24-h recovery period. Confocal images are captured [Cell Voyager CV7000 (Yokogawa, Japan)] and analysed using Columbus software (PerkinElmer). As standard the assay detects micronuclei (MN), cytotoxicity and cell-cycle profiles from Hoechst phenotypes. Mode of action information is primarily determined by kinetochore labelling in MN (aneugencity) and γH2AX foci analysis (a marker of DNA damage). Applying computational approaches and implementing machine learning models alongside Bayesian classifiers allows the identification of, with 95% accuracy, the aneugenic, clastogenic and negative compounds within the data set (Matthews correlation coefficient: 0.9), reducing analysis time by 80% whilst concurrently minimising human bias. Combining high throughput screening, multiparametric image analysis and machine learning approaches has provided the opportunity to revolutionise early Genetic Toxicology assessment within AstraZeneca. By multiplexing assay endpoints and minimising data generation and analysis time this assay enables complex genotoxicity safety assessments to be made sooner aiding the development of safer drug candidates.